Molecular chaperones, which are present in all organisms and are highly conserved, are known to interact with proteins to mediate protein folding, assembly, disassembly and remodeling without themselves being part of the final complex. To understand these interactions is of fundamental biological significance and also of medical relevance, as aberrant folding reactions have emerged as the cause of a number of inherited diseases. An exciting recent development in cell biology is the increasing number of findings that implicate molecular chaperones, both directly and indirectly, in protein degradation. Although researchers have begun to assess the role of molecular chaperones in proteolysis, the mechanisms by which the cellular machineries for folding and degradation interact are largely unknown. We have been investigating the role of ClpA, the regulatory component of the ClpAP protease, in both protein remodeling and degradation. We discovered that alone it is an ATP-dependent molecular chaperone, able to activate the latent DNA binding activity of plasmid P1 RepA by converting RepA dimers into monomers. In combination with ClpA it degrades RepA. To understand the interrelationship between the chaperone function of ClpA and its function in proteolysis, we have used biochemical techniques to isolate and characterize intermediates in the degradation reaction. We dicovered that there is not a preferred order of assembly of intermediate complexes; preassembled ClpA-ClpP complexes can bind substrate and preassembled ClpA-substrate complexes can bind ClpP. In both cases, formation of substrate-ClpA-ClpP complexes requires ATP binding but not hydrolysis. Interestingly, the substrate is reduced to acid soluble polypeptides following a single round of binding to ClpAP followed by ATP hydrolysis. Our current model of the degradation pathway is that ClpA targets the substrate for degradation by its interaction with the substrate and then unfolds and translocates the polypeptide to the ClpP active sites, where proteolysis occurs. The similarities between the mechanism of protein remodeling by chaperones and the mechanism of the early steps of degradation by ATP-dependent proteases suggest the possibility that the ATPase components of proteases may particpate with classical chaperones in the kinetic partitioning of non-native proteins between pathways leading to reactivation, degradation or aggregation.